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Updated: Aug 13, 2025
13:41
Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus
Published on: March 8, 2012
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Beta human papillomavirus 8E6 promotes alternative end joining.
Changkun Hu1,2, Taylor Bugbee2, Rachel Palinski3
1Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States.
Elife
|January 24, 2023
Summary
Beta-human papillomavirus (HPV8 E6) protein promotes alternative end joining (Alt-EJ) DNA repair by interacting with p300. This leads to increased genomic instability and deletions, potentially driving cancer formation.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Double-strand breaks (DSBs) are critical DNA lesions.
- Beta-human papillomavirus E6 (HPV8 E6) protein disrupts homologous recombination (HR) and non-homologous end joining (NHEJ) DNA repair pathways.
- The precise mechanism of DSB repair modulation by HPV8 E6 remains unclear.
Purpose of the Study:
- To investigate how DSBs are repaired in cells expressing HPV8 E6.
- To determine if HPV8 E6 promotes alternative end joining (Alt-EJ) DNA repair.
- To elucidate the role of p300 in HPV8 E6-mediated DNA repair.
Main Methods:
- Utilized CRISPR/Cas9-based Alt-EJ reporters.
- Employed small molecule inhibitors and gene knockout strategies.
- Analyzed whole genome sequencing data to assess mutational consequences.
Main Results:
- HPV8 E6 was shown to promote Alt-EJ DNA repair.
- HPV8 E6 facilitates Alt-EJ by binding to the acetyltransferase p300.
- Whole genome sequencing revealed increased deletions with Alt-EJ microhomology signatures.
Conclusions:
- HPV8 E6 promotes the less common Alt-EJ pathway for DSB repair.
- HPV8 E6-mediated p300 destabilization contributes to genomic instability.
- This mechanism supports the hypothesis that beta-HPV promotes cancer via increased genomic instability.
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